The ojbective of this research is to evaluate the mechanisms which prevent the immune system from controlling malignant cell growth. Three potentially important mechanisms will be examined. First, the role of class I histocompatibility antigen expression by tumor cells in generating immunity will be evaluated using a spontaneous murine lung tumor, line 1, which fails to express these normal antigens. Radiation treatment appears to induce expression of these antigens, which may have important implications for the immune response to this tumor, subsquent to radiotherapy. Second, it is known that the presence of hypoxic cells within tumors is a limiting feature in effective radiation treatment. This hypoxia, which exists because many tumors outgrow the blood supply, is similar to that found within multicellular tumor spheroids, a model system which has many characteristics of in vivo solid tumors. We will use this model to determine whether hypoxia also affects the function of cytolytic T lymphocytes. Third, we have identified an immunoinhibitory factor (IIF) produced by a spontaneous murine mammary tumor, EMT6 which inhibits the proliferation of both B and T cells. We will further characterize the functional and biochemical properties of this factor and determine its in vivo significance.